Theories which account for renal medullary handling of solutes and water frequently neglect the role of the microcirculation. In contrast, recent studies revealed unique vasa recta transport properties as well as the existence of water channels and a facilitated urea transporter in the outer medullary descending vasa recta (OMDVR). The overall object of these studies is to obtain further information on the magnitude and regulation of those properties and to incorporate that information into models of medullary physiology. We will employ methods for in vivo microperfusion of inner medullary descending (IMDVR) and ascending vasa recta (IMAVR) and for in vitro microperfusion of OMDVR from rat vascular bundles to accomplish the following specific objectives. 1. To determine the pathways and mechanisms responsible for transport of water across OMDVR. The hypothesis that water is transported across OMDVR by paracellular and cellular pathways will be tested. Osmotic water permeability of these pathways will be measured. Experiments will verify and quantitate the role of water channels by examining Arrhenius activation energy, mercurial inhibition and quantitation of aquaporin CHIP by fluorescent ELISA. 2. To measure the permselectivity of descending and ascending vasa recta by measuring transport of labeled dextran probes. 3. To verify preliminary data that solute transport in OMDVR is regulated by the separate effects of pericyte constriction and modulation of the urea transporter. Hormonal actions of vasoconstrictors and vasopressin on urea and sodium transport will be examined. The effects of pre-existing diuretic state and osmolality on solute and water transport will also be determined. 4. To employ the measurements from aims 1-4 to complete a mathematical simulation of microvascular exchange in the renal medulla. The model will account for paracellular and cellular transport pathways and simulate exchange of middle molecular weight solutes and albumin.